Professor's breast cancer research focuses on protein
For Dunbar, this research is personal.
"I had a very good friend die of breast cancer when I was in graduate school," Dunbar explains. "She suffered for fifteen years with the disease and died just before her fiftieth birthday."
Her research over the past decade has involved studying the role of a particular protein, PTHrP (parathyroid hormone-related protein), and its association with normal development of the mammary gland, the organ present in mammals that produces milk for the young. By studying the effect of too much or too little PTHrP, a more complete understanding of the maturation of the mammary gland is possible. As the maturation process becomes clear, problems associated with PTHrP may help us better understand breast cancer.
Dunbar explains that the mammary gland is actually a specialized sebaceous gland containing milk-producing structures called alveoli. The aveoli are embedded in a cushion of fat to help protect the gland. Each alveolus (the singular of aveoli) connects to a duct through which the milk flows until it is secreted through the nipple of the breast.
A mammal may have one or multiple (up to eleven pairs) of mammary glands, depending on the species. All humans have two breasts. The glands in both sexes are premature until puberty when, under the influence of ovarian hormones, the glands begin to develop in females. During pregnancy the mammary ducts grow and develop further in preparation for producing milk for the young. The maturation of the mammary gland involves continual secretion of cellular signals helping to regulate that growth; PTHrP is one of those signals.
Two tissues involved in normal mammary gland development are the epithelial and mesenchymal, with PTHrP serving a messenger between the two tissues to deliver information sent by estrogen. This small protein appears to function as a negative regulator of estrogen-induced growth during puberty.
As part of Dunbar's collaboration with Yale University, her laboratory has been studying a genetically engineered mouse strain that overproduces PTHrP in the mammary glands. These mice have defects in mammary development during puberty that appear to be the result of abnormal estrogen signaling in the mammary gland. Experiments are currently ongoing to unravel the mechanisms by which PTHrP may regulate estrogen- induced growth of the mammary gland.
Many published results have implicated estrogen as a potential carcinogen for breast tissue, so the interaction of PTHrP with estrogen in the mammary glands could lead to a better understanding of how this tissue becomes cancerous. Recent findings in breast cancer research have indicated that a woman's risk for breast cancer increases the longer she delays childbirth. This increased risk appears to be due to the fact that the immature cells of the pre- or non-pregnant breast are more susceptible to the cancer-causing effects of estrogen. The fact that PTHrP appears to be involved at this critical stage of breast development could lead to a better understanding, and potential treatment, for breast cancer.
The role of PTHrP in mammary development can also be studied using a cell culture model. Undergraduate students at Penn State Berks have developed a cell culture system to study the effects of estrogen and PTHrP on mammary cell growth. Using these cultured mammary cells, the students have identified several factors that may act in concert with PTHrP to regulate mammary cell growth.
Findings from student research have been presented at national meetings and have been published in professional journals.
"The excitement that undergraduates exhibit when they generate a novel finding is one of the most gratifying aspects of my job," comments Dunbar. "Students learn in a way that cannot be replicated in the classroom. They learn invaluable skills such as teamwork, communication, and confidence. The time I spend with students engaged in research is always time well spent."
"The research performed in my laboratory is aimed at better defining the role of PTHrP in normal mammary gland development. My hope is that this work will ultimately result in improved treatments for breast cancer, but for now I remain focused on the interaction of PTHrP within the epithelial and mesenchymal tissues. My students and I enjoy the small victories that result from basic research, as well as the camaraderie that results from working on a team toward a larger goal."